{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:19Z","timestamp":1785417379674,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170898"],"award-info":[{"award-number":["32170898"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32170898"],"award-info":[{"award-number":["32170898"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research on Health Beneficial Bacteria and Metabolites to Enhance Military Operational Capability","award":["GCCRC-2024-002"],"award-info":[{"award-number":["GCCRC-2024-002"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1305404"],"award-info":[{"award-number":["2023YFF1305404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023T160641"],"award-info":[{"award-number":["2023T160641"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2023T160641"],"award-info":[{"award-number":["2023T160641"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hospital\u2019s \u201c3 + 1\u201d Innovative Talent Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>LL-37, a 37-amino acid human-derived antimicrobial peptide, was shown in our earlier clinical study to shorten the negative conversion time of the Omicron BA.5.1.3 variant of SARS-CoV-2. In this work, we investigated the broad mechanism of LL-37 by examining its inhibitory effect on non-enveloped virus Enterovirus 71 (EV71). LL-37 treatment dose-dependently reduced EV71 viral RNA abundance, suppressed virus-encoded protein expression, and decreased infectious titers, acting predominantly at a post-entry stage of the viral life cycle. Transcriptomic analysis revealed that the SH3 and cysteine-rich domain protein (Stac) was uniquely upregulated by LL-37 irrespective of EV71 infection. Short hairpin RNA (shRNA)-mediated Stac silencing significantly enhanced EV71 infection, while Stac overexpression markedly reduced it. Furthermore, we found that LL-37 activates the EGFR\u2013ERK signaling pathway, leading to time-dependent upregulation of Stac expression. These findings uncover a novel host-directed mechanism by which LL-37 combats EV71 infection and suggests a potential therapeutic use of LL-37 against non-enveloped viral disease.<\/jats:p>","DOI":"10.3390\/v18040442","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:40:31Z","timestamp":1775554831000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LL-37 Inhibits EV71 Infection by Upregulating STAC via the EGFR-ERK Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Jiaqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-1859","authenticated-orcid":false,"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhuang","family":"Peng","sequence":"additional","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0003-1195","authenticated-orcid":false,"given":"Zhe","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1010-9195","authenticated-orcid":false,"given":"Yujian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-8602","authenticated-orcid":false,"given":"Meng","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhu","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Sun","sequence":"additional","affiliation":[{"name":"Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1968258","DOI":"10.1080\/19490976.2021.1968258","article-title":"IL-27 induces LL-37\/CRAMP expression from intestinal epithelial cells: Implications for immunotherapy of Clostridioides difficile infection","volume":"13","author":"Xu","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1039\/b912533g","article-title":"The chemistry and biology of LL-37","volume":"26","author":"Burton","year":"2009","journal-title":"Nat. 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